5-HT1A 受体拮抗剂11C-WAY-100635的自动化合成

doi:10.7538/tws.2016.youxian.036

摘要/Abstract

摘要：

为自动化合成用于5-羟色胺(5-HT_1A)受体显像¹¹C标记的N-［2-［4-(2-甲氧基苯基)-1-哌嗪基］乙基］-N-2-吡啶基环己烷甲酰胺（¹¹C-WAY-100635），采用自动化合成模块，以去甲基WAY-100635为前体，经甲基化，HPLC纯化和Sep-Pak Plus C18柱去除有机溶剂制得¹¹C-WAY-100635注射液。结果显示，合成方法共耗时约40 min，¹¹C-WAY-100635注射液的未校正放化产率10%~20%，放化纯度>97%；静脉注射日本大耳白兔¹¹C-WAY-100635（约111 MBq）后，脑组织放射性摄取显著，且明显高于头颅等其他组织。自动化合成5-HT_1A受体显像剂¹¹C-WAY-100635方法简单，反应时间较短，放化纯度高，产率稳定可靠，可在临床中推广应用。

关键词:

¹¹C-WAY-100635, 自动化合成, HPLC分离

Abstract:

A fully automated synthesis of ¹¹C-labeled-N-［2-［4-(2-methoxyphenyl)-1-piperazinyl］ethyl］-N-2-pyridinylcyclohexanecarboxamide maleate (¹¹C-WAY-100635) for imaging 5-HT_1A receptors was performed on a module system. ¹¹C-WAY-100635 was obtained based on the methylation reaction of the precursor (O-demethyl)-WAY-100635, purification with HPLC and subsequent removal of organic solvents using a Sep-Pak Plus C18. The results revealed that fully automated synthesis of ¹¹C-WAY-100635 was completed within the total synthesis time of about 40 min. The uncorrected radiochemical yield was between 10% and 20%, and the radiochemical purity was over 97%. After the intravenous injection of ¹¹C-WAY-100635 (about 111 MBq), the uptake in the brain tissues of the white rabbit was significantly higher than the other tissues of head. This method provides simple synthesis of ¹¹C-WAY-100635 with relatively short radiosynthesis time and a high radiochemical yield for clinical need.

Key words:

¹¹C-WAY-100635, automated synthesis, HPLC purification

李会强;甄志飞;张伟峰;廖曙光;李宏利;徐俊玲. 5-HT_1A 受体拮抗剂¹¹C-WAY-100635的自动化合成[J]. 同位素, 2017, 30(2): 119-124.

LI Hui-qiang;ZHEN Zhi-fei;ZHANG Wei-feng;LIAO Shu-guang;LI Hong-li;XU Jun-ling. Automated Synthesis of 5-HT_1A Receptors Antagonists ¹¹C-WAY-100635[J]. Journal of Isotopes, 2017, 30(2): 119-124.

参考文献

［1］Peroutka S J. 5-Hydroxytryptamine receptors［J］. Journal of Neurochemistry, 1993, 60(2): 408-416.
［2］刘飞，贺佑丰，罗志福. 中枢神经系统5-羟色胺受体显像剂WAY类似物的研究进展［J］. 同位素,2001,14(1):41-49(in Chinese).Liu fei, He youfeng, Luo zhifu. Development progress of WAY analogues in CNS 5-hydroxytrypamine receptor imaging agents［J］. Journal of Isotopes, 2001, 14(1): 41-49(in Chinese).
［3］Shen Y, Monsma F J, Metcalf M A. Molecular cloning and expression of a 5-hydroxytrypamine7 serotonin receptor subtype［J］. Journal of Biological Chemistry, 1993, 268(24): 18200-18204.
［4］Middlemiss D N, Fozard J R. 8-hydroxy-2 (di-n-propylamino)-tetralin discriminated between subtypes of 5-HT_1A recognition site［J］. European Journal of Pharmacology, 1983, 90(1): 151-153.
［5］陆春雄，吴春英，蒋泉福. 5-HT_1A受体拮抗剂WAY-100635的合成［J］. 中国医药工业杂志，2005,36(7):391-392.Lu chunxiong, Wu chunying, Jiang Quanfu. Synthesis of 5-HT_1A receptor antagonist WAY-100635［J］. Chinese Journal of Pharmaceuticals, 2005, 36(7): 391-392(in Chinese).
［6］Ian A C. A retrospect on the discovery of WAY-100635 and the prospect for improved 5-HT_1A receptor PET radioligands［J］. Nuclear Medicine &Biology. 2000, 27: 441-447.
［7］Farde L. The advantage of using positron emission tomography in drug research［J］. Trends Neurosci. 1996, 19(6): 211-214.
［8］Glenmon R A. Central serotonin receptors as targets for drug research［J］. Journal of Medical Chemistry, 1987, 30: 1-12.
［9］Glenmon R A, Naiman N A, Pierson M E. N-(phthanlimidoalkyl) aerrvatires of serotonergic agents: a common interaction at 5-HT_1A serotonin binding sites?［J］. Journal of Medical Chemistry. 1989, 32(8): 1921-1926.
［10］Victor W P, Julie A M, Suan P H. et al. Pre-clinical development of a radioligand for studies of central 5-HT_1A Receptors in vivo-［¹¹C］-WAY-100635［J］. Medicinal Chemistry Research, 1994, 5: 208-227.
［11］张锦明，田嘉禾，姚树林，等. ¹¹C-Raclopride的快速制备及生物学评价［J］. 中华核医学杂志，2008,28(4):227-230.Zhang jinming, Tian jiahe, Yao shulin, et al. Fast synthesis of ¹¹C-Raclopride and its initial PET study on animal model［J］. Chinese Journal of Nuclear Medicine. 2008, 28(4): 227-230(in Chinese).
［12］Gao M, Gao A, Wang M, et al. Synthesis of carbon-11-labeled aminoalkylindole derivatives as new candidates of cannabinoid receptor radioligands for PET imaging of alcohol abuse［J］. Bioorganic & Medicinal Chemistry Letters. 2014, 24(24): 5581-5586.
［13］Gao M, Wang M, Green M A, et al. Synthesis of ［¹¹C］-GSK1482160 as a new PET agent for targeting P2X₇ receptror［J］. Bioorganic & Medicinal Chemistry Letters, 2015, 25(9): 1965-1970. 
［14］Krasikova R, Fedorova O, Korsakov M, et al. A fast and convenient method for robtic preparation of ¹¹C-flumazenil avoiding HPLC purification［J］. Journal of Labeled Compounds & Radiopharmaceuticals, 2000, 43: 613-621.
［15］Wang M, Gao M, Miller K D, et al. Synthesis of ［¹¹C］PBR06 and ［¹⁸F］PBR06 as agents for position emission tomographic (PET) imaging of the translocator protein (TSPO)［J］. Steroids, 2011, 76(12): 1331-1340.
［16］许莉莉. 5-HT1A受体及其与抑郁症相关性的研究进展［J］. 中国医药导报，2012,9(3):16-17,20.Xu lili. Progress of correlation study between 5-HT_1A receptor and depression［J］. China Medical Herald, 2012, 9(3): 16-17, 20(in Chinese).

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5-HT_1A 受体拮抗剂¹¹C-WAY-100635的自动化合成

Automated Synthesis of 5-HT_1A Receptors Antagonists ¹¹C-WAY-100635

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